Actuation systems and methods

ABSTRACT

Actuation systems and methods are disclosed. An apparatus includes a system including a flow cell receptacle and a valve drive assembly including a shape memory alloy actuator including a pair of shape memory alloy wires and a flow cell disposable within the flow cell receptacle and having a membrane valve. The system actuates the membrane valve, via the shape memory alloy actuator, by causing a voltage to be applied to a first one of the shape memory alloy wires and the system not applying the voltage to a second one of the shape memory alloy wires.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.18/087,274, filed Dec. 22, 2022, which is a continuation of US PatentApplication Number 17/529,059, filed Nov. 17, 2021, which itself claimsthe benefit of and priority to U.S. Provisional Patent Application No.63/116,765, filed Nov. 20, 2020, the content of each of which isincorporated by reference herein in its entireties and for all purposes.

BACKGROUND

Fluidic cartridges carrying reagents and a flow cell are sometimes usedin connection with fluidic systems. The fluidic cartridge may befluidically coupled to the flow cell. The fluidic cartridges includefluidic lines through which the reagents flow to the flow cell.

SUMMARY

Shortcomings of the prior art can be overcome and advantages andbenefits as described later in this disclosure can be achieved throughthe provision of actuation systems and methods. Various implementationsof the apparatus and methods are described below, and the apparatus andmethods, including and excluding the additional implementationsenumerated below, in any combination (provided these combinations arenot inconsistent), may overcome these shortcomings and achieve theadvantages and benefits described herein.

In accordance with a first implementation, an apparatus includes a shapememory alloy actuator assembly having a housing including a pair oflateral sides, each having a first end and a second end and a transversesection coupling the lateral walls. A printed circuit board is coupledto the first end of the housing, an end plate is coupled to the secondend of the housing, and a plurality of shape memory alloy actuators arepositioned between the printed circuit board and the end plate. Eachshape memory alloy actuator includes a pair of wire mounts coupled toopposing sides of the printed circuit board, an actuator rod ispositioned between the lateral sides of the housing and includes a wireguide and a shape memory alloy wire coupled to the wire mounts andpositioned around the wire guides. Applying a voltage to the shapememory alloy wire retracts the shape memory alloy wire and causes thecorresponding actuator rod to move between a first position and a secondposition.

In accordance with a second implementation, an apparatus includes asystem including a flow cell receptacle and a valve drive assemblyincluding a shape memory alloy actuator including a pair of shape memoryalloy wires and a flow cell disposable within the flow cell receptacleand having a membrane valve. The system actuates the membrane valve viathe shape memory alloy actuator by causing a voltage to be applied to afirst one of the shape memory alloy wires and the system not applyingthe voltage to a second one of the shape memory alloy wires.

In accordance with a third implementation, an apparatus includes asystem including a valve drive assembly including plurality of shapememory alloy actuators and a flow cell assembly including a flow cellinlet, a flow cell outlet, a flow cell, and a manifold assembly. Themanifold assembly includes a common fluidic line having a first side anda second side. The flow cell is coupled to the common fluidic line, aplurality of reagent fluidic lines are disposed on the second side ofthe common fluidic line, and a plurality of membrane valves areselectively fluidically couple the common fluidic line and acorresponding one of the plurality of reagent fluidic lines. Each shapememory alloy actuator corresponds to one of the membrane valves and isactuatable to selectively control a flow of reagent between each of thereagent fluidic lines and the common fluidic line.

In accordance with a fourth implementation, an apparatus includes ashape-memory alloy actuator including a guide defining an aperture andincluding wire mounts. An actuator rod is movable through the apertureand includes a plunger at a distal end, a wire guide, and a spring seat.A spring is positioned between the guide and the spring seat. A shapememory alloy wire is coupled to the wire mounts and is positioned aroundthe wire guide. Applying a voltage to the shape memory alloy wireretracts the shape memory alloy wire and causes the actuator rod to movebetween a first position and a second position.

In accordance with a fifth implementation an apparatus includes a shapememory alloy actuator assembly including a housing, a printed circuitboard, a plurality of shape memory alloy actuators, and an actuatormanifold assembly. The housing includes a pair of lateral sides eachhaving a first end and a second end and a transverse section couplingthe lateral sides. The printed circuit board is coupled to the first endof the housing and the plurality of shape memory alloy actuators arepositioned between the printed circuit board and the second end. Eachshape memory alloy actuator includes a pair of wire mounts, an actuatorrod, and a shape memory alloy wire. The pair of wire mounts are coupledto opposing sides of the printed circuit board and the actuator rod ispositioned between the lateral walls of the housing and includes a wireguide. The actuator rod includes a side port and an end face having avacuum port and a plunger portion. The side port is fluidically coupledto the vacuum port. The shape memory alloy wire is coupled to the wiremounts and is positioned around the wire guide. The actuator manifoldassembly is coupled to the printed circuit board and includes a body anda plurality of pneumatic lines. The body has an outlet port and aplurality of inlet ports and each pneumatic line is coupled between theside ports of the actuator rods and the inlet ports of the actuatormanifold assembly. Applying a voltage to the shape memory alloy wireretracts the shape memory alloy wire and causes the correspondingactuator rod to move between a first position and a second position.

In accordance with a sixth implementation, an apparatus includes asystem having a flow cell receptacle and a plurality of shape memoryalloy actuators.

In accordance with a seventh implementation, a method includes causing avoltage to be applied to a first one of shape memory alloy wires of ashape memory alloy actuator and not applying the voltage to a second oneof the shape memory alloy wires of the shape memory alloy actuator. Themethod also includes responsive to applying the voltage to the first oneof the shape memory alloy wires, actuating a membrane valve with theshape memory alloy actuator.

In accordance with an eighth implementation, a method includes sealinglyengaging a portion of a membrane of a membrane valve with a vacuum portof an actuator rod of a shape memory alloy actuator and causing avoltage to be applied to a shape memory alloy wire of the shape memoryalloy actuator. The method also includes responsive to applying thevoltage to the shape memory alloy wire, moving the actuator rod and theportion of the membrane between a first position and a second position.

In further accordance with the foregoing first, second, third, fourth,fifth, a sixth, seventh, and/or eighth implementations, an apparatusand/or method may further comprise or include any one or more of thefollowing:

In an implementation, the apparatus further includes an enclosuresurrounding the housing and defining one or more vents positioned toenable air flow (air or gas) across the shape memory alloy wires.

In another implementation, the vents are elongate openings extendingrelative to one or more of the shape memory alloy wires.

In another implementation, the enclosure has open sides.

In another implementation, the apparatus further includes an air flowassembly to flow air across the shape memory alloy wires.

In another implementation, the air flow assembly includes a fan.

In another implementation, the shape memory alloy actuator assembly is afirst shape memory alloy actuator assembly and the apparatus furtherincludes a second shape memory alloy actuator assembly opposing thefirst shape memory alloy actuator assembly.

In another implementation, each of the plurality of shape memory alloyactuators of the first shape memory alloy actuator assembly apply apulling force and each of a plurality of shape memory alloy actuators ofthe second shape memory alloy actuator apply a pushing force.

In another implementation, the pulling force is less than the pushingforce.

In another implementation, the apparatus further includes a plurality ofbiasing elements positioned to bias the actuator rods toward the firstposition.

In another implementation, the first position is a closed position of anassociated valve.

In another implementation, the first position is an open position of anassociated valve.

In another implementation, the biasing elements are positioned betweenthe printed circuit board and spring seats of the actuator rods.

In another implementation, the end of each actuator rod defines abiasing rod aperture. A biasing rod is positioned in the correspondingbiasing rod apertures and extends toward the biasing element. A bushingis positioned around each biasing rod and is positioned to interact withthe corresponding biasing element.

In another implementation, the biasing elements include leaf springs.

In another implementation, the transverse section includes a pluralityof lateral guide slots and each actuator rod is positioned in acorresponding lateral guide slot.

In another implementation, the lateral guide slots include first lateralguide slots defined on a first side of the transverse section and secondlateral guide slots defined on a second side of the transverse section.

In another implementation, the first lateral guide slots are staggeredrelative to the second lateral guide slots.

In another implementation, the transverse section defines a plurality ofguide rod apertures and each actuator rod includes a guide rod thatextends through a corresponding guide rod aperture.

In another implementation, the guide rod apertures are staggered betweenthe lateral sides.

In another implementation, each actuator rod includes a plunger portionarranged to actuate an associated valve.

In another implementation, each actuator rod includes a body, theplunger portion, and one or more lateral guides coupled between the bodyand the plunger portion.

In another implementation, the one or more lateral guides include a pairof opposing lateral guides.

In another implementation, the end plate defines a plurality of slotspositioned to receive the plunger portions.

In another implementation, each actuator rod defines a transverse wireguide through which a corresponding shape memory alloy wire extends.

In another implementation, the transverse wire guide includes a curvedsurface.

In another implementation, the system includes a counter that counts anumber of instances that the system causes the voltage to be applied tothe first one of the shape memory alloy wires and the system causes thevoltage to be applied to the second one of the shape memory alloy wiresand to not be applied to the first one of the shape memory alloy wireswhen the number of instances satisfies a reference number.

In another implementation, the system tests operability of the first oneof the shape memory alloy wires and causes the voltage to be applied tothe second one of the shape memory alloy wires and to not be applied tothe first one of the shape memory alloy wires when the system identifiesthe first one of the shape memory alloy wires being inoperable.

In another implementation, the system includes a fan mounted to thesystem to cool the shape memory alloy wires and spaced from the shapememory alloy actuator to deter vibration from the fan from beingimparted to the shape memory alloy actuator.

In another implementation, the fan is operable at a first speed when theflow cell and the associated membrane valve are spaced a first distancefrom the fan and operable at a second speed when the flow cell and theassociated membrane valve are spaced a second distance from the fan.

In another implementation, the membrane valves are volcano valves.

In another implementation, each shape memory alloy actuator includes aplunger, a spring that biases the plunger, and a shape memory alloywire.

In another implementation, actuating the shape memory alloy actuatorincludes the system causing a voltage to be applied to the shape memoryalloy wire that retracts the plunger against a force of the spring.

In another implementation, each of the shape memory alloy actuatorsinclude a pair of shape memory alloy wires and actuating the shapememory alloy actuator includes the system causing a voltage to beapplied to a first one of the shape memory alloy wires and the systemnot applying the voltage to a second one of the shape memory alloywires.

In another implementation, the shape memory alloy wire is a first shapememory alloy wire and the actuator rod includes a second wire guide. Asecond shape memory alloy wire is coupled to the wire mounts and ispositioned around the second wire guide.

In another implementation, the voltage is applied to the first shapememory alloy wire to actuate the shape-memory alloy actuator whenvoltage is not applied to the second shape memory alloy wire.

In another implementation, further including applying a voltage to thesecond shape memory alloy wire when voltage is not applied to the firstshape memory alloy wire.

In another implementation, the voltage is not applied to the first shapememory alloy wire after a threshold amount of time, after a thresholdnumber of cycles, or if the first shape memory alloy wire is damaged.

In another implementation, the shape memory alloy wire is a first shapememory alloy wire, the guide is a first guide, and the actuator rodincludes a second wire guide. The apparatus also includes a second guidehaving wire mounts and a second shape memory alloy wire is coupled tothe wire mounts of the second guide and positioned around the secondwire guide.

In another implementation, further including applying voltage to thefirst and second wires at substantially the same time.

In another implementation, further including applying voltage to thefirst and second wires in parallel.

In another implementation, applying the voltage to the first shapememory alloy wire retracts the first shape memory alloy wire and causesthe actuator rod to move between the first position and the secondposition and applying a voltage to the second shape memory alloy wireretracts the second shape memory alloy wire and causes the actuator rodto move between the second position and the first position.

In another implementation, the plurality of shape memory alloy actuatorsincludes a first row of shape memory alloy actuators and a second row ofthe shape memory alloy actuators, the shape memory alloy actuators ofthe first row being staggered relative to the shape memory alloyactuators of the second row.

In another implementation, the plurality of shape memory alloy actuatorsincludes first shape memory alloy actuators on a first side of the flowcell receptacle and second shape memory alloy actuators on a second sideof the flow cell receptacle.

In another implementation, the first shape memory alloy actuators opposethe second shape memory alloy actuators.

In another implementation, the first shape memory alloy actuators applya pulling force and the second shape memory alloy actuators apply apushing force.

In another implementation, the pulling force is less than the pushingforce.

In another implementation, the system includes a fan positioned to flowair toward the plurality of shape memory alloy actuators.

In another implementation, the apparatus includes an enclosuresurrounding the shape memory alloy wires.

In another implementation, the enclosure has a first enclosure assemblyand a second enclosure assembly, each of the first enclosure assemblyand the second enclosure assembly has an enclosure body coupled to thehousing and has an inlet port assembly.

In another implementation, the inlet port assembly has an inlet port anda diffuser.

In another implementation, the inlet port assembly further includes apressure homogenizer and a nozzle array. The pressure homogenizerpositioned between the nozzle array and the diffuser and the diffuserpositioned between the pressure homogenizer and the inlet port.

In another implementation, axes of nozzles of the nozzle array aresubstantially parallel to an axis of the inlet port.

In another implementation, each shape memory alloy actuator includes asensor or a target carried by the actuator rod and the housing carriesthe other of the sensor or the target.

In another implementation, the apparatus includes a flow cell assemblyincluding a flow cell inlet, a flow cell outlet, a flow cell, and amanifold assembly. The manifold assembly includes a common fluidic line,a plurality of reagent fluidic lines, and a plurality of membranevalves. The flow cell is coupled to the common fluidic line and themembrane valves are selectively fluidically couple the common fluidicline and a corresponding one of the plurality of reagent fluidic lines.Each membrane valve has a body and a membrane coupled to a surface ofthe body. The body includes a valve seat and defines a chamberfluidically coupled to the corresponding reagent fluidic line andcovered by a portion of the membrane.

In another implementation, opening the membrane valves includes thevacuum port of the corresponding shape memory actuator sealinglyengaging the portion of the membrane and moving between the firstposition and the second position.

In another implementation, each shape memory alloy actuator includes asensor or a target carried by the actuator rod and each membrane valvecarries the other of the sensor or the target.

In another implementation, responsive to a distance between the sensorand the target being greater than a threshold value, the shape memoryalloy actuator causes the actuator rod to move toward the portion ofmembrane and for the vacuum port of the corresponding shape memoryactuator to sealing engage the portion of the membrane.

In another implementation, the chamber and the portion of the membranehave a width greater than a width of the valve seat.

In another implementation, the chamber and the portion of the membraneare squircle shaped.

In another implementation, the chamber and the portion of the membraneare tear-drop shaped.

In another implementation, closing the membrane valves includes theplunger portion of the corresponding shape memory actuator moving themembrane from the second position to the first position and urging themembrane into engagement with the valve seat.

In another implementation, each of the actuator rods includes a secondside port and the end face has a second vacuum port. The plunger portionis positioned between the vacuum port and the second vacuum port.

In another implementation, each membrane valve defines a second chambercovered by a second portion of the membrane. The valve seat ispositioned between the chamber and the second chamber.

In another implementation, opening the membrane valves includes thesecond vacuum port of the corresponding shape memory actuator sealinglyengaging the second portion of the membrane and moving between the firstposition and the second position.

In another implementation, the pneumatic lines of the actuator manifoldassembly are coupled between a second side port of the actuator rods andcorresponding inlet ports of the actuator manifold assembly.

In another implementation, the method includes counting a number ofinstances that the voltage is applied to the first one of the shapememory alloy wires and causing the voltage to be applied to the secondone of the shape memory alloy wires and to not be applied to the firstone of the shape memory alloy wires when the number of instancessatisfies a reference number.

In another implementation, the method includes testing operability ofthe first one of the shape memory alloy wires.

In another implementation, the method includes identifying the first oneof the shape memory alloy wires being inoperable and causing the voltageto be applied to the second one of the shape memory alloy wires and tonot be applied to the first one of the shape memory alloy wires afteridentifying the first one of the shape memory alloy wires beinginoperable.

In another implementation, the method includes cooling the shape memoryalloy wires.

In another implementation, the method includes cooling the shape memoryalloy wires comprises using a fan.

In another implementation, the method includes deterring vibrations fromthe fan from being imparted to the shape memory alloy actuator.

In another implementation, the method includes identifying a distancebetween the actuator rod and a membrane valve being greater than athreshold value and, responsive to the distance between the actuator rodand the membrane valve being greater than the threshold value, causingthe actuator rod to move toward the portion of the membrane and for thevacuum port of the shape memory actuator to sealing engage the portionof the membrane.

In another implementation, the method includes closing the membranevalve by moving the portion of the membrane from the second position tothe first position using a plunger portion of the actuator rod andurging the portion of the membrane into engagement with a valve seat ofthe membrane valve.

It should be appreciated that all combinations of the foregoing conceptsand additional concepts discussed in greater detail below (provided suchconcepts are not mutually inconsistent) are contemplated as being partof the subject matter disclosed herein and/or may be combined to achievethe particular benefits of a particular aspect. In particular, allcombinations of claimed subject matter appearing at the end of thisdisclosure are contemplated as being part of the subject matterdisclosed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic diagram of an implementation of a systemin accordance with the teachings of the present disclosure.

FIG. 2 is a cross-sectional view of an implementation of the manifoldassembly of FIG. 1 with the associated valve in the closed position.

FIG. 3 is a cross-sectional view of the implementation of the manifoldassembly of FIG. 2 with the associated valve in the open position.

FIG. 4 is a top view of an example implementation of a manifold assemblyand a flow cell including membrane valves positioned on a first side ofa common reagent fluidic line and membrane valves positioned on a secondside of the common fluidic line.

FIG. 5A is an isometric view of an example implementation of the valvedrive assembly, the manifold assembly, and the flow cell that can beused to implement the valve drive assembly of FIGS. 1, 2, and 3 .

FIG. 5B is another isometric view of the valve drive assembly and themanifold assembly of FIG. 5A.

FIG. 5C is a top cross-sectional schematic illustration of the firstactuator assembly of FIG. 5A.

FIG. 6 is an isometric view of another example implementation of thevalve drive assembly, the manifold assembly, and the flow cell that canbe used to implement the valve drive assembly of FIGS. 1, 2, and 3 .

FIG. 7 is an isometric detailed view of an interface between the firstactuator assembly and the second actuator assembly of FIG. 6 .

FIG. 8A is an isometric view of the first actuator assembly of FIG. 6showing a plurality of biasing elements positioned to bias the actuatorrods toward the first position.

FIG. 8B shows an enclosure surrounding the wires of the actuatorassembly of FIG. 6 .

FIG. 8C shows a partial cross-sectional view of the second enclosureassembly of the enclosure of FIG. 8B taken along line 8C-8C of FIG. 8B.

FIG. 9 is an isometric view of the first actuator assembly of FIG. 6 .

FIG. 10 is an isometric view of a plurality of the biasing elements ofthe first actuator assembly of FIG. 6 .

FIG. 11 is an isometric view of the housing and the actuator rods of thefirst actuator assembly of FIG. 6 .

FIG. 12 is an isometric view of the actuator rods of the first actuatorassembly of FIG. 6 .

FIG. 13 is an isometric view of the housing and the end plate showingthe slots that receive the lateral guides of the actuator rods of thefirst actuator assembly of FIG. 6 .

FIG. 14 is a side view of the actuator rods and the end plate of thefirst actuator assembly of FIG. 6 .

FIG. 15 is a cross-sectional expanded view of an alternativeimplementation of the membrane of the manifold assembly and the actuatorrod of the first and/or second actuator assemblies of FIG. 5A or any ofthe disclosed implementations.

FIG. 16 is a cross-sectional expanded view of an alternativeimplementation of the membrane and the actuator rod of the first and/orsecond actuator assemblies of FIG. or any of the disclosedimplementations.

FIG. 17 is a cross-sectional expanded view of an alternativeimplementation of the membrane and the actuator rod of the first and/orsecond actuator assemblies of FIG. or any of the disclosedimplementations.

FIG. 18 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators in a first positionthat can be used to implement the actuators of FIG. 5A.

FIG. 19 illustrates a cross-sectional view of the shape memory alloyactuator of FIG. 18 in a second position.

FIG. 20 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators that can be used toimplement the actuators of FIG. 5A.

FIG. 21 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators that can be used toimplement the actuators of FIG. 5A.

FIG. 22 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators that can be used toimplement the actuators of FIG. 5A.

FIG. 23 illustrates an isometric view of the second actuator assembly ofFIG. 6 showing plunger portions of the actuator rods extending through aprinted circuit board and being actuatable to interface with anassociated manifold assembly.

FIG. 24 illustrates another isometric view of the second actuatorassembly of FIG. 6 showing a housing, a plurality of actuator rods, anda circuit board.

FIG. 25 illustrates another isometric view of a plurality of actuatorrods including spring seats of the second actuator assembly of FIG. 6 .

FIG. 26 is a top view of another example implementation of the manifoldassembly of FIG. 1 .

FIG. 27 is a bottom view of the manifold assembly of FIG. 26 .

FIG. 28 is an isometric view of an example valve drive assembly that canbe used to implement the valve drive assembly of FIGS. 1, 2, and 3

FIG. 29 is an isometric view of the printed circuit board and aplurality of shape memory alloy actuators of the actuator assembly ofFIG. 28 .

FIG. 30 is a top view of an example flow cell assembly including amanifold assembly and a flow cell that can be used to implement the flowcell assembly of FIG. 1 .

FIG. 31 is an isometric view of a portion of an example valve driveassembly that can be used to implement the valve drive assembly of FIGS.1, 2, and 3 .

FIG. 32 is an isometric view of the valve drive assembly of FIG. 31including an actuator manifold assembly coupled to the printed circuitboard and including a body and fluidic lines.

FIG. 33 is a detailed view of the end face of one of the actuator rodsincluding the first and second vacuum ports with the plunger portionpositioned between the vacuum ports 432.

FIG. 34 is a top view of an example flow cell assembly including amanifold assembly and a flow cell that can be used to implement the flowcell assembly of FIG. 1 .

DETAILED DESCRIPTION

Although the following text discloses a detailed description ofimplementations of methods, apparatuses and/or articles of manufacture,it should be understood that the legal scope of the property right isdefined by the words of the claims set forth at the end of this patent.Accordingly, the following detailed description is to be construed asexamples only and does not describe every possible implementation, asdescribing every possible implementation would be impractical, if notimpossible. Numerous alternative implementations could be implemented,using either current technology or technology developed after the filingdate of this patent. It is envisioned that such alternative exampleswould still fall within the scope of the claims.

It may be advantageous or beneficial to have valve actuators thatprovide accurate and precise dispensing of small volumes of fluids (forexample, liquid reagents), which in some instances may be pressurized,while maintaining a small overall footprint, including width, height,and depth.

This disclosure is directed toward valve drive assemblies of a system(for example, a sequencing system) that interfaces with a reagentcartridge and a flow cell assembly including membrane valves. The systemincludes a shape memory alloy (SMA) actuator and the membrane valves arepart of a manifold assembly. The SMA actuators may be positioned veryclose to one another on a circuit board—10 millimeters (mm) or lessspacing. The use of SMA actuators advantageously allows the membranevalves to be spaced more closely together (minimal footprint), therebyreducing an amount of dead volume within the fluidic network. Forexample, the SMA actuators as disclosed allow the membrane valves to bespaced in a manner that reduces dead volume between the reagent fluidiclines and a common fluidic line. Less consumables such as reagents maybe used as a result. Moreover, by spacing the membranes valves closertogether, a length of a common reagent line may be reduced, therebyshortening cycle times and run times of instruments/systems implementingthe disclosed examples.

The SMA actuators include a plunger, a spring that biases the plunger,and a SMA wire in some implementations. The SMA actuator is actuated byapplying a voltage to the SMA wire, which retracts the SMA wire and theplunger against a force of the spring. In other implementations, the SMAactuators each include a pair of SMA wires, where one of the SMA wiresis actuated at a time to increase the useful life of the SMA actuator.The system may actuate the SMA actuator by causing voltage to be appliedto a first one of the SMA wires while not applying the voltage to asecond one of the SMA wires as an example. If the system identifies thatthe first one of SMA wires is used a threshold number of times or is nolonger operable, the system may actuate the SMA actuator by causingvoltage to be applied to the second one of the SMA wires to actuate theSMA actuator while not applying the voltage to the first one of the SMAwires.

FIG. 1 illustrates a schematic diagram of an implementation of a system100 in accordance with the teachings of the present disclosure. Thesystem 100 can be used to perform an analysis on one or more samples ofinterest. The sample may include one or more DNA clusters that arelinearized to form a single stranded DNA (sstDNA). In the implementationshown, the system 100 includes a reagent cartridge receptacle 102 thatcan receive a reagent cartridge 104. The reagent cartridge 104 carries aflow cell assembly 106.

The system 100 includes, in part, a drive assembly 108, a controller110, an imaging system 112, and a waste reservoir 114 in theimplementation shown. The drive assembly 108 includes a pump driveassembly 116 and a valve drive assembly 118 and an air flow assembly 120arranged to flow air over one or more components of the system 100including, for example, the valve drive assembly 118. The air flowassembly 120 may be mounted to the system 100 in a manner that reducesvibration and may be operated at a first speed when the valve driveassembly 118 is positioned a first distance from the air flow assembly120 and may be operated at a second speed when the valve drive assembly118 is positioned a second distance from the air flow assembly 120. Theair flow assembly 120 may not be directly mounted to the valve driveassembly 118 as doing so would impart more vibration from the air flowassembly 120 to the valve drive assembly 118.

Referring back to the controller 110, in the implementation shown, thecontroller 110 is electrically and/or communicatively coupled to thedrive assembly 108, the imaging system 112, and the air flow assembly120 and can cause the drive assembly 108, the imaging system 112, and/orthe air flow assembly 120 to perform various functions as disclosedherein. The waste reservoir 114 may be selectively receivable within awaste reservoir receptacle 122 of the system 100. In otherimplementations, the waste reservoir 114 may be included in the reagentcartridge 104.

The reagent cartridge 104 may carry one or more samples of interest. Thedrive assembly 108 interfaces with the reagent cartridge 104 to flow oneor more reagents (e.g., A, T, G, C nucleotides) that interact with thesample through the reagent cartridge 104 and/or through the flow cellassembly 106.

In an implementation, a reversible terminator is attached to the reagentto allow a single nucleotide to be incorporated by the sstDNA per cycle.In some such implementations, one or more of the nucleotides has aunique fluorescent label that emits a color when excited. The color (orabsence thereof) is used to detect the corresponding nucleotide. Theimaging system 112 can excite one or more of the identifiable labels(e.g., a fluorescent label) and thereafter obtain image data for theidentifiable labels in the implementation shown. The labels may beexcited by incident light and/or a laser and the image data may includeone or more colors emitted by the respective labels in response to theexcitation. The image data (e.g., detection data) may be analyzed by thesystem 100. The imaging system 112 may be a fluorescencespectrophotometer including an objective lens and/or a solid-stateimaging device. The solid-state imaging device may include a chargecoupled device (CCD) and/or a complementary metal oxide semiconductor(CMOS).

After the image data is obtained, the drive assembly 108 interfaces withthe reagent cartridge 104 to flow another reaction component (e.g., areagent) through the reagent cartridge 104 that is thereafter receivedby the waste reservoir 114 and/or otherwise exhausted by the reagentcartridge 104. The reaction component performs a flushing operation thatchemically cleaves the fluorescent label and the reversible terminatorfrom the sstDNA. The sstDNA is then ready for another cycle.

The flow cell assembly 106 includes a housing 124 and a flow cell 126.As used herein, a “flow cell” can include a device having a lidextending over a reaction structure to form a flow channel there betweenthat is in communication with a plurality of reaction sites of thereaction structure, and can include a detection device that detectsdesignated reactions that occur at or proximate to the reaction sites.The flow cell 126 includes at least one channel 128, a flow cell inlet130, and a flow cell outlet 132. The channel 128 may be U-shaped or maybe straight and extend across the flow cell 126. Other configurations ofthe channel 128 may prove suitable. Each of the channels 128 may have adedicated flow cell inlet 130 and a dedicated flow cell outlet 132. Asingle flow cell inlet 130 may alternatively be fluidly coupled to morethan one channel 128 via, for example, an inlet manifold. A single flowcell outlet 132 may alternatively be coupled to more than one channelvia, for example, an outlet manifold. In an implementation, the flowcell assembly 106 may be formed by a plurality of layers such as, forexample, laminate layers. The flow cell 126 and/or the channel 128 mayinclude one or more microstructures or nanostructures in such animplementation. The microstructures may be formed using a nanoimprintlithography pattern or embossing. Other manufacturing techniques mayprove suitable. The nanostructures may include wells, pillars,electrodes, gratings, etc.

In the implementation shown, the reagent cartridge 104 includes a flowcell receptacle 134, a common fluidic line 136, a plurality of reagentfluidic lines 138, and a manifold assembly 139. In otherimplementations, the manifold assembly 139 is part of the flow cellassembly 106 and/or part of the system 100. The reagent cartridge 104includes a reagent cartridge body 140.

The flow cell receptacle 134 can receive the flow cell assembly 106. Theflow cell assembly 106 can alternatively be integrated into the reagentcartridge 104. In such implementations, the flow cell receptacle 134 maynot be included or, at least, the flow cell assembly 106 may not beremovably receivable within the reagent cartridge 104. The flow cellassembly 106 may in some implementations be separate from the reagentcartridge 104 and receivable in the flow cell receptacle 134 of thesystem 100.

Each of the reagent fluidic lines 138 can be coupled to a correspondingreagent reservoir 142 that may contain fluid (e.g., reagent and/oranother reaction component). The reagent cartridge body 140 may beformed of solid plastic using injection molding techniques and/oradditive manufacturing techniques. The reagent reservoirs 142 areintegrally formed with the reagent cartridge body 140 in someimplementations. The reagent reservoirs 142 are separately formed andare coupled to the reagent cartridge body 140 in other implementations.

In the implementation shown, the manifold assembly 139 includes aplurality of membrane valves 144 and a plurality of actuators 146disposed within the manifold assembly 139. In other implementations, oneor more of the actuators 146 may be excluded. The membrane valves 144may be rod-flap valves or volcano valves. The manifold assembly 139fluidically couples the common fluidic line 136 and each of the reagentfluidic lines 138. Each membrane valve 144 is coupled between the commonfluidic line 136 and a corresponding reagent fluidic line 138. Theactuators 146 may alternatively be omitted.

The valve drive assembly 118 interfaces with the actuators 146 and/orthe membrane valves 144 in operation to control a flow of reagentbetween the reagent fluidic lines 138 and the common fluidic line 136.In some implementations and as further disclosed below, the valve driveassembly 118 includes a plurality of shape memory alloy actuators thatare selectively actuatable to control a position of the correspondingactuators 146 and/or membrane valves 144. Shape memory alloy actuatorsare moved between a first position and a second position (actuated) byapplying a voltage to a shape memory alloy wire, which causes thetemperature of the wire to increase and for the wire to contract. Whenthe voltage is no longer applied to the wire, the temperature of thewire decreases and the wire relaxes. To increase the rate at which thetemperature of the wire decreases, in the implementation shown, thesystem 100 includes the air flow assembly 120 that flows air over thewires to increase heat dissipation and decrease an amount of time forthe wires to move from contracted position to the relaxed position. Theair flow assembly 120 can be one or more fans or another source of airsuch as a pressurized air source (e.g., the pressure source of FIG. 1 ).A single larger fan may be used or, alternatively, a plurality ofsmaller fans may be used in some implementations. The air flow assembly120 may decrease the rate at which the wires cool or relax byapproximately 7.3 times. The air flow assembly 120 may flow air over thewires while the system 100 is operating and/or when the shape memoryalloy actuators are actuating.

Referring now to the manifold assembly 139, in the implementation shown,the manifold assembly 139 includes a manifold body 148 that may beformed of polypropylene, a cyclic olefin copolymer, a cyclo olefinpolymer, and/or other polymers. The manifold body 148 defines a portion150 of the common fluidic line 136 and a portion 152 of the reagentfluidic lines 138. A membrane 154 is coupled to portions 156 of themanifold body 148 while another portion 157 of the membrane 154 is notcoupled to the manifold body 148. The membrane 154 may thus be locallybonded to the manifold body 148 while the portion 157 above a valve seat158 of the manifold body 148 is not being bonded to the membrane 154 toallow for a fluidic passage to be created. The membrane 154 may beformed of a flat sheet. The membrane 154 may be elastomeric.

The membrane valves 144 are formed by the membrane 154 and the manifoldbody 148 in the implementation shown. The manifold body 148 includes thevalve seat 158 disposed between the portions 156 of the manifold body148 and the valve seat 158 is not coupled to the membrane 154. Themembrane 154 may thus move away from the valve seat 158 to allow fluidto flow across the corresponding membrane valve 144. The actuators 146may move the membrane 154 away from the valve seat 158 when actuated toallow fluid flow through the corresponding membrane valve 144. Using theactuators 146 may be advantageous when fluid is drawn across themembrane valve 144 using, for example, negative pressure (e.g., asyringe pump). The membrane 154 may move away from the valve seat 158 inother implementations responsive to a positive pressure of reagentallowing for the actuators 146 to be omitted.

To close the membrane valves 144, the valve drive assembly 118interfaces with the membrane 154 and drives the membrane 154 against thevalve seat 158. The valve drive assembly 118 may allow the membrane 154to move away from the valve seat 158 to open the membrane valves 144. Inan implementation where the valve drive assembly 118 includes aplurality of plungers, the plungers may selectively move away from thevalve seat 158 to allow the membrane 154 to move away from the valveseat 158. In another implementation, the valve drive assembly 118includes plungers that are coupled to the membrane 154. The couplingbetween the plungers and the membrane 154 may be a snap fit connectionor a magnetic connection. Other types of couplings may prove suitable.For example, the valve drive assembly 118 may be mechanically linked tothe membrane 154.

The manifold assembly 139 includes a shut-off valve 160 in theimplementation shown that may interface with the valve drive assembly118 and may further control the flow between at least one of the reagentfluidic lines 138 and the common fluidic line 136. The shut-off valve160 may be actuated to the closed position after processes using reagentfrom a corresponding reagent reservoir 142 are complete, for example.The shut-off valve 160 may be positioned upstream or downstream of arespective membrane valve 144. Such an approach may further detercross-contamination from occurring between the different reagents.Because there is a reduced likelihood of cross-contamination, less washbuffer may be used.

The system 100 includes a pressure source 162 that may, in someimplementations, be used to pressurize the reagent cartridge 104. Thereagent, under pressure via the pressure source 162, may be urgedthrough the manifold assembly 139 and toward the flow cell assembly 106.The pressure source 162 may be carried by the reagent cartridge 104 inanother implementation. A regulator 164 is positioned between thepressure source 162 and the manifold assembly 139 and regulates apressure of the gas provided to the manifold assembly 139. The gas maybe air, nitrogen, and/or argon. Other gases may prove suitable.Alternatively, the regulator 164 and/or pressure source 162 may not beincluded.

Referring now to the drive assembly 108, in the implementation shown,the drive assembly 108 includes the pump drive assembly 116 and thevalve drive assembly 118. The pump drive assembly 116 can interface withone or more pumps 166 to pump fluid through the reagent cartridge 104.The pump 166 may be implemented by a syringe pump, a peristaltic pump, adiaphragm pump, etc. While the pump 166 may be positioned between theflow cell assembly 106 and the waste reservoir 114 the pump 166 may bepositioned upstream of the flow cell assembly 106 or omitted entirely inother implementations.

Referring to the controller 110, in the implementation shown, thecontroller 110 includes a user interface 168, a communication interface170, one or more processors 172, and a memory 174 storing instructionsexecutable by the one or more processors 172 to perform variousfunctions including the disclosed implementation. The user interface168, the communication interface 170, and the memory 174 areelectrically and/or communicatively coupled to the one or moreprocessors 172.

In an implementation, the user interface 168 can receive input from auser and to provide information to the user associated with theoperation of the system 100 and/or an analysis taking place. The userinterface 168 may include a touch screen, a display, a key board, aspeaker(s), a mouse, a track ball, and/or a voice recognition system.The touch screen and/or the display may display a graphical userinterface (GUI).

In an implementation, the communication interface 170 can enablecommunication between the system 100 and a remote system(s) (e.g.,computers) via a network(s). The network(s) may include the Internet, anintranet, a local-area network (LAN), a wide-area network (WAN), acoaxial-cable network, a wireless network, a wired network, a satellitenetwork, a digital subscriber line (DSL) network, a cellular network, aBluetooth connection, a near field communication (NFC) connection, etc.Some of the communications provided to the remote system may beassociated with analysis results, imaging data, etc. generated orotherwise obtained by the system 100. Some of the communicationsprovided to the system 100 may be associated with a fluidics analysisoperation, patient records, and/or a protocol(s) to be executed by thesystem 100.

The one or more processors 172 and/or the system 100 may include one ormore of a processor-based system(s) or a microprocessor-based system(s).In some implementations, the one or more processors 172 and/or thesystem 100 includes one or more of a programmable processor, aprogrammable controller, a microprocessor, a microcontroller, a graphicsprocessing unit (GPU), a digital signal processor (DSP), areduced-instruction set computer (RISC), an application specificintegrated circuit (ASIC), a field programmable gate array (FPGA), afield programmable logic device (FPLD), a logic circuit, and/or anotherlogic-based device executing various functions including the onesdescribed herein.

The memory 174 can include one or more of a semiconductor memory, amagnetically readable memory, an optical memory, a hard disk drive(HDD), an optical storage drive, a solid-state storage device, asolid-state drive (SSD), a flash memory, a read-only memory (ROM),erasable programmable read-only memory (EPROM), electrically erasableprogrammable read-only memory (EEPROM), a random-access memory (RAM), anon-volatile RAM (NVRAM) memory, a compact disc (CD), a compact discread-only memory (CD-ROM), a digital versatile disk (DVD), a Blu-raydisk, a redundant array of independent disks (RAID) system, a cache,and/or any other storage device or storage disk in which information isstored for any duration (e.g., permanently, temporarily, for extendedperiods of time, for buffering, for caching).

FIG. 2 is a cross-sectional view of an implementation of the manifoldassembly 139 including the membrane valve 144 and the valve driveassembly 118 of FIG. 1 . The membrane valve 144 is a rod flap valve thatis in the closed position in the implementation shown and the valvedrive assembly 118 includes portions on both sides of the manifoldassembly 139. The valve drive assembly 118 thus interfaces with themembrane valve 144 on a first side 175 of the manifold assembly 139 andthe actuator 146 on a second side 176 of the manifold assembly 139.

The manifold assembly 139 includes the manifold body 148 and opposingmembranes 154, 177 coupled to the manifold body 148 in theimplementation shown. The actuator 146 is captured between the opposingmembranes 154, 177 that also form a portion of the reagent fluidic line138. The membranes 154 and/or 177 may have a thickness of approximately1 millimeter (mm). Other thicknesses however may prove suitable.

The actuator 146 is a cantilever having a distal end 180 movablerelative to the membranes 154, 177 and a proximal end 182 coupled to themanifold body 148 in the implementation shown. The manifold body 148includes a concave cutout 188 adjacent the distal end 180 of theactuator 146 that allows the membrane 177 to be urged, via the valvedrive assembly 118, in a direction generally indicated by arrow 184without putting stress on the membrane 177 in a manner that may damagethe membrane 177. The actuator 146 can be actuated in operation, via thevalve drive assembly 118, to move the distal end 180 in a directiongenerally indicated by arrow 184 between an extended position and aretracted position, as shown. The distal end 180 can thus move themembrane 154 away from the corresponding valve seat 158 responsive tobeing engaged by a valve plunger 186 of the valve drive assembly 118.

The valve drive assembly 118 positioned on the bottom of the manifoldassembly 139 relative to the orientation shown in FIG. 2 actuates themembrane valve 144. The membrane valve 144 is shown in the closedposition with the valve plunger 186 in the extended position urging themembrane 154 against the valve seat 158.

FIG. 3 is another cross-sectional view of the implementation of themanifold assembly 139 of FIG. 2 with the associated membrane valve 144in the open position. The valve drive assembly 118 above the manifoldassembly 139 as shown interfaces with the membrane 177 to move theactuator 146 and the opposing membrane 154 away from the valve seat 158.The valve drive assembly 118 below the manifold assembly 139 is spacedfrom the membrane 154 to allow fluid flow between the membrane 154 andthe valve seat 158.

FIG. 4 is a top view of an example flow cell assembly 195 including amanifold assembly 196 and the flow cell 126 that can be used toimplement the flow cell assembly 106 of FIG. 1 . The flow cell assembly195 includes the membrane valves 144 positioned on a first side 190 ofthe common fluidic line 136 and the membrane valves 144 positioned on asecond side 192 of the common fluidic line 136. The membrane valves 144are opened in operation and reagent is flowed to the flow cell 126 andtoward an outlet 194 associated with the waste reservoir 114. Themembrane valves 144 may be spaced approximately 4 millimeters (mm)apart. For example, the membrane valves 144 on each side of the commonreagent fluidic line 136 may be spaced approximately 4 mm apart (a pitchbetween the centers of the membrane valves 144 of approximately 4 mm),thereby enabling a length of the common fluidic line 136 to be reduced.

FIG. 5A is an isometric view of an example implementation of the valvedrive assembly 118, the manifold assembly 139, and the flow cell 126that can be used to implement the valve drive assembly 118 of FIGS. 1,2, and 3 . The valve drive assembly 118 includes a first shape memoryalloy actuator assembly 200 positioned to interface with the membranevalves 144 on the first side 175 of the manifold assembly 139 and asecond shape memory alloy actuator assembly 202 opposing the firstactuator assembly 200 and positioned to interface with the manifoldassembly 139 on the second side 176 of the manifold assembly 139 in theimplementation shown. A backing plate 205 is shown coupled to themanifold assembly 139 that deters the manifold assembly 139 from bendingwhen the membrane valves 144 are being actuated. The first actuatorassembly 200 may have a height of approximately 85 millimeters (mm) andthe second manifold assembly 202 may have a height of approximately 89mm. Either of the first and/or second actuator assemblies 200, 202however may have any suitable height including the same height.

In the implementation shown, the first actuator assembly 200 includes ahousing 204 including a pair of lateral sides 206 each having a firstend 208 and a second end 210 and a transverse section 212 coupling thelateral sides 206. The housing 204 may be a H-shaped frame and thelateral sides 206 may be lateral walls of the H-shaped frame. While thehousing 204 is shown as a frame, the housing 204 may include one or moresolid blocks or pieces of material that define actuator rod bores. Thefirst actuator assembly 200 also includes a printed circuit board 214coupled to the first end 208 of the housing 204 and an end plate 216coupled to the second end 210 of the housing 204. The end plate 216 ofthe first actuator assembly 200 is positioned immediately adjacent themanifold assembly 139 and the printed circuit board 214 is spaced fromthe manifold assembly 139. The end plate 216 of the second actuatorassembly 202 in contrast is spaced from the manifold assembly 139 whilethe printed circuit board 214 is positioned immediately adjacent themanifold assembly 139.

The first actuator assembly 200 also includes a plurality of shapememory alloy actuators 218 positioned between the printed circuit board214 and the end plate 216. Each actuator 218 includes a pair of wiremounts 220 coupled to opposing sides 222, 224 of the printed circuitboard 214 in the implementation shown and an actuator rod 226 positionedbetween the lateral sides 206 of the housing 204 and including a wireguide 228. The actuators 218 also include a shape memory alloy wire 230coupled to the wire mounts 220 and positioned through the wire guide228. The wire 230 may have a 60 um wire diameter and may include anultra-pure alloy. While each of the first actuator assembly 200 and thesecond actuator assembly 202 are shown including seven actuators 218,any number of actuators 218 may be included and the first actuatorassembly 200 may have the same number of actuators 218 or a differentnumber of actuators 218 than the second actuator assembly 200.

Referring still to the first actuator assembly 200, a plurality ofbiasing elements 231 are positioned to bias the actuator rods 226 towardthe first position. In the implementation shown, the biasing elements231 are positioned between the printed circuit board 214 and a springseat 233 of the actuator rods 226 and urge the actuator rods 226 towardthe manifold assembly 139, causing the associated membrane valves 144 toclose. The biasing elements 231 are shown as coil springs but othertypes of biasing elements may be used. Belleville washers, torsionsprings, leaf springs, etc. may be used, for example. Moreover, whilethe biasing elements 231 are shown surrounding the actuator rods 226 andseated against the spring seat 233 of the actuator rods 226, the biasingelements 231 may be differently arranged. Ends of the actuator rods 226may include the spring seat and the biasing elements 231 may bepositioned between the printed circuit board 214 and the ends of theactuator rods 226, for example . While the actuator rods 226 of thefirst actuator assembly 200 are urged toward the manifold assembly 139,the biasing elements 231 of the second actuator assembly 202 arepositioned to urge the actuator rods 226 away from the manifold assembly139, enabling the associated membrane valve 144 to close and/or for theactuator 146 to move to the non-actuated position (See, FIG. 2 ).

To actuate the actuators 218 of the first actuator assembly 200 in adirection generally indicated by arrow 232 and move the actuator rods226 away from the associated membrane valves 144, a voltage is appliedto the wire 230 that retracts the wire 230 and causes the correspondingactuator rod 226 to move between a first position and a second position.A distance between the first and second positions may be approximately0.8 millimeters (mm). Different stroke lengths however are achievable.Moreover, using the first and second actuator assemblies 200, 202, themembrane valves 144 can be moved between an open position and a closedposition in approximately less than 90 milliseconds. Advantageously andbased on the faster cycle times of the membrane valves 144, smallervolumes of reagent such as, for example, approximately 24 μL can bedispensed when the reagent is being moved under positive pressure.

Energizing the wire 230 of the first actuator assembly 200 in someimplementations applies a force of approximately 2.4 Newton (N) to theactuators 218 in the direction generally indicated by arrow 232 andenergizing the wire 230 of the second actuator assembly 202 applies aforce of approximately 3.7 N to the actuators 218 in the directiongenerally indicated by arrow 232. Other forces however may be achieved.The actuators 218 of the first actuator assembly 200 may be used to urgethe membrane 154 against the valve seat 158 and the actuators 218 of thesecond actuator assembly 202 may be used to move the actuator 146 of therod-flap valve (see, FIG. 3 ) of the manifold assembly 139.

In some implementations, pulse width modulation (PWM) is tuned andapplied for approximately 45 milliseconds (ms) to, for example, enablethe membrane valves 144 to be opened and/or closed relatively rapidly,while reducing vibration. Lesser amounts of power may be applied to thewire 230 in some implementations, causing the wire 230 to move from thefirst position to the second position more slowly but increasing therate at which the wire 230 moves from the second position back to thefirst position (e.g., increased cooling rate). Moreover, differentdiameter wires 230 may be used to increase or decrease the cooling timeof the wire 230 have voltage is applied thereto.

While the above-description describes the first actuator assembly 200,the second actuator assembly 202 has similar structure and can beoperated in a similar manner. However, in contrast, applying voltage tothe wires 230 of the second actuator assembly 202 moves the actuatorrods 226 toward the associated membrane valves 144 and, thus, also inthe direction generally indicated by arrow 232. Put another way,actuating the first actuator assembly 200 pulls the actuator rods 226away from the manifold assembly 139 and actuating the second actuatorassembly pushes the actuator rods 226 toward the manifold assembly 139.Moreover, because the actuator rods 226 of second actuator assembly 202may be used to actuate the actuator 146 captured within the manifoldassembly 139, the second actuator assembly 202 may generate a largeramount of force as compared to the amount for force generated by thefirst actuator assembly 200 to hold the membrane 154 against the valveseat 158.

FIG. 5B is another isometric view of the valve drive assembly 118 andthe manifold assembly 139 of FIG. 5A. The manifold assembly 139 isoriented such that ports 234 that are used to flow regent to the reagentfluidic lines 138 are viewable in the implementation shown. FIG. 5B alsoshows that both the first and second actuator assemblies 200, 202 havean enclosure 236, 238 surrounding the housing 204. The enclosures 236,238 define one or more vents 240 positioned to enable air flow acrossthe wires 230. The vents 240 may be defined on opposing sides of theenclosures 236, 238 or, more generally, may be defined on one or moresides of the enclosures 236, 238. The vents 240 advantageouslyconcentrate air flowing from, for example, the air flow assembly 120 tomore rapidly reduce the temperature of the wires 230 and allow thecorresponding actuator 218 to move back to the relaxed position. Thevents 240 are shown being elongate openings 242 that extend relative toone or more of the wires 230. The vents 240 however may be any shapeand/or any size. Sides 237 of the enclosure 236, 238 may additionally beopen. As such, air can flow freely through the enclosures 236, 239 in adirection generally indicated by arrow 239 and through and around aspace defined by the wires 230.

FIG. 5C is a top cross-sectional schematic illustration of the firstactuator assembly 200 of FIG. 5A. The transverse section 212 includes aplurality of lateral guide slots 292 in the implementation shown andeach actuator rod 226 is positioned in a corresponding lateral guideslot 292. First lateral guide slots 296 are defined on a first side 298of the transverse section 212 and second lateral guide slots 300 aredefined on a second side 301 of the transverse section 212. The firstlateral guide slots 296 are staggered relative to the second lateralguide slots 300 in the implementation shown to enable the actuator rods226 to interface with a staggered arrangement of membrane valves 144such as the valve arrangement shown in FIG. 4 .

FIG. 6 is an isometric view of another example implementation of thevalve drive assembly 118, the manifold assembly 139, and the flow cell126 that can be used to implement the valve drive assembly 118 of FIGS.1, 2, and 3 . The valve drive assembly 118 of FIG. 6 is similar to thevalve drive assembly 118 of FIG. 5A. However, in contrast, the actuatorrods 226 of the valve drive assembly 118 of FIG. 6 include a pair oflateral wire guides 228.

FIG. 7 is an isometric detailed view of an interface 243 between thefirst actuator assembly 200 and the second actuator assembly 202 of FIG.6 . The actuator rods 226 include plunger portions 244, 246, with theplunger portions 244 of the first actuator assembly 200 having flat ends248 and the plunger portions 246 of the second actuator assembly 202having rounded ends 250 in the implementation shown.

FIG. 8A is an isometric view of the first actuator assembly 200 of FIG.6 showing a plurality of switches 252 positioned to be tripped when theactuator rods 226 are in the second position. When one of the switches252 is tripped, further flow of electricity to the corresponding wire230 is reduced allowing the wire 230 to stay in the second position, butat a reduced temperature than before. In turn, this enables the wire 230to return to the first position faster once the first position iscommanded (otherwise the temperature difference (delta) from the firstposition to the second position would be higher due to higherelectricity flow, thereby hindering quickly switching from position oneto position two). In the implementation shown, the switches 252 arepositioned between the printed circuit board 214 and ends 254 of theactuator rods 226.

FIG. 8B shows an enclosure 800 surrounding the wires 230 of the firstactuator assembly 200 of FIG. 6 . The enclosure 800 has a firstenclosure assembly 802 positioned on a first side 806 of the housing 204and a second enclosure assembly 804 positioned on a second side 808 ofthe housing 204. Each of the enclosure assemblies 802, 804 has anenclosure body 810 coupled to the housing 204 and has an inlet portassembly 812. The enclosure bodies 810 taper from the inlet portassemblies 812 toward the end plate 216 of the housing 204, therebydirecting the flow of fluid (e.g., air or gas) in a direction generallyindicated by arrows 811, 813. As shown, the end plate 216 is a flangethat is integral with the housing 204. The end plate 216 mayalternatively be coupled to the housing 204.

The inlet port assemblies 812 each have an inlet port 814 in theimplementation shown that may be fluidly coupled to the air flowassembly 120 that flows fluid into the inlet port 814 and over the wires230 to increase heat dissipation. Flowing fluid over the wires 230 alsodecreases an amount of time for the wires 230 to move from thecontracted position to the relaxed position, by, for example, 50% or,more specifically, to about 33.7 milliseconds (ms), 48.4 ms, 54.4 ms,56.0 ms. The inlet port assemblies 812 homogenizes the flow within theenclosures assemblies 802 and/or 804 and/or homogenizes the pressurewithin the enclosure assemblies 802, 804.

FIG. 8C shows a partial cross-sectional view of the second enclosureassembly 804 taken along line 8C-8C of FIG. 8B. The second enclosureassembly 804 includes the inlet port 814, a diffuser 816, a pressurehomogenizer 818, and a nozzle array 820 having a plurality of nozzles822. The nozzle array 820 is a rectangular array including nozzles 822.One or more of the nozzles 822 (two of the nozzles 802) may be adjacentto an external side 821 of the second enclosure assembly 804 and spacedfrom the A different number and/or a different arrangement of nozzles822 may be included.

The pressure homogenizer 818 is positioned between the nozzle array 820and the diffuser 816 and the diffuser 816 is positioned between thepressure homogenizer 818 and the inlet port 814 and axes of nozzles 822of are shown substantially parallel to an axis of the inlet port 814.The axis of the inlet port 814 may alternatively be at an angle such assubstantially perpendicular to the axes of the nozzles 822. The axes ofthe nozzles 822 and the axis of the inlet port 814 may be differentlyarranged. As set forth herein, substantially parallel means about 5° ofparallel including parallel itself and substantially perpendicular meansabout 5° of perpendicular including perpendicular itself.

FIG. 9 is an isometric view of the first actuator assembly 200 of FIG. 6. The ends 254 of each actuator rod 226 define a rod aperture 256 in theimplementation shown. A rod 258 is positioned in a corresponding rodaperture 256 and extends toward the switch 252. The rod aperture 256 maybe a blind bore such that the rod 258 can move the switch 252 toward theprinted circuit board 214. A bushing 260 may be positioned around eachrod 258 and positioned to interact with the corresponding switch 252. Insuch examples, the rod 258 can be used to retain the position of thebushing 260 relative to the actuator rod 226 and the bushing 260 can beused to transfer the force of the switch 252 to the actuator rod 226.

FIG. 10 is an isometric view of a plurality of the switches 252 of thefirst actuator assembly 200 of FIG. 6 . The switches 252 are leafsprings 262 having a pair of prongs 264 that can be used to couple theswitches 252 to the printed circuit board 214 in the implementationshown. An end 266 of the leaf springs 262 are positioned to engage acontact of the printed circuit board 214 and cause the correspondingswitch 252 to be tripped. The position of the leaf springs 262 is basedon the corresponding position of the actuator rods 226. An engagementportion 290 of some of the leaf springs 262 are thus arranged to bepositioned adjacent (e.g., beneath) the first side 222 of the printedcircuit board 214 and the engagement portion 290 of others of the leafsprings 262 are arranged to be positioned relatively adjacent the secondside 224 of the printed circuit board 214.

FIG. 11 is an isometric view of the housing 204 and the actuator rods226 of the first actuator assembly 200 of FIG. 6 . The transversesection 212 includes a plurality of lateral guide slots 292 in theimplementation shown and each actuator rod 226 has a leg 294 positionedin a corresponding lateral guide slot 292, where first lateral guideslots 296 are defined on a first side 298 of the transverse section 212and second lateral guide slots 300 are defined on a second side 301 ofthe transverse section 212. The first lateral guide slots 296 arestaggered relative to the second lateral guide slots 300 in theimplementation shown. The transverse section 212 defines a plurality ofguide rod apertures 302 and each actuator rod 226 includes a guide rod304 that extends through a corresponding guide rod aperture 302.Interaction between the guide rod 304 and the surface of the transversesection 212 defining the guide rod apertures 302 guides the relativemovement of the actuator rod 226. The guide rod apertures 302 arestaggered between the lateral sides 206.

FIG. 12 is an isometric view of the actuator rods 226 of the firstactuator assembly 200 of FIG. 6 . Each of the actuator rods 226 includesa body 306, the plunger portion 244, and one or more lateral guides 308coupled between the body 306 and the plunger portion 244 in theimplementation shown. The lateral guide 308 of FIG. 12 includes a pairof opposing lateral guides 308 that are sized to be received bycorresponding slots 310 (See, FIG. 13 ) defined by the end plate 216.

FIG. 13 is an isometric view of the housing 204 and the end plate 216showing the slots 310 that receive the lateral guides 308 of theactuator rods 226. The slots 310 in the implementation shown arestaggered and include rectangular portions 312 that receive the lateralguides 308 and are positioned on either side of a circular centralportion 314 that receive the plunger portions 244 of the actuator rods226.

FIG. 14 is a side view of the actuator rods 226 and the end plate 216 ofthe first actuator assembly 200 of FIG. 1 . Each actuator rod 226defines a transverse wire guide 316 through which a corresponding wire230 extends in the implementation shown. The transverse wire guide 316has a curved surface 318 against which the wire 230 engages to reducewear. Each of the lateral wire guides 228 as also shown defines a slot320 including a curved surface 322 against which the wire 230 engages toreduce wear.

FIG. 15 is a cross-sectional expanded view of an alternativeimplementation of the membrane 154 of the manifold assembly 139 and theactuator rod 226 of FIG. 5A or any of the disclosed implementations. Theactuator rod 226 is coupled to the membrane 154 in the implementationshown. The actuator rod 226 includes a male portion 324 and the membrane154 includes a female portion 326. The female portion 326 is defined byan arrow shaped blind bore. The cross-section of the male portion 324corresponds to the cross-section of the female portion 326.

The male portion 324 as shown is received by the female portion 326. Asnap fit connection is formed between the actuator rod 226 and themembrane 154. When the actuator rod 226 is moved in a directiongenerally indicated by arrow 328, the coupling between the actuator rod226 and the membrane 154 physically moves the membrane 154 in generallythe same direction. The reagent may thus not be pressurized in someimplementations and the actuator rod 226 can pull the membrane 154 awayfrom the valve seat 158 such that a pump can push and/or pull reagentinto the common fluidic line 136.

FIG. 16 is a cross-sectional expanded view of an alternativeimplementation of the membrane 154 and the actuator rod 226 of FIG. 5Aor any of the disclosed implementations. The actuator rod 226 is coupledto the membrane 154 in the implementation shown. The actuator rod 226includes a first magnet 330 and the male portion 324 includes a secondmagnet 332. The first magnet 330 is attracted to the second magnet 332such that moving the actuator rod 226 correspondingly moves the membrane154. As an alternative, one of the first magnet 330 or the second magnet332 can be a magnet and the other can include a material (aferromagnetic material) that is attracted to the magnet. The secondmagnet 332 in some implementations can be embedded and/or impregnated inthe membrane 154.

FIG. 17 is a cross-sectional expanded view of an alternativeimplementation of the membrane 154 and the actuator rod 226 that can beused to implement the actuators 218 of FIG. 5A or any of the actuatorsdisclosed herein. The actuator rod 226 is coupled to the membrane 154 inthe implementation shown. The actuator rod 226 includes the male portion324 and the membrane 154 includes the female portion 326. In contrast tothe implementation of FIG. 15 , a snap fit connection is not formed whenthe male portion 324 is received by the female portion 326. The femaleportion 326 includes inwardly tapering sides 334 that correspond toinwardly tapering sides 336 of the male portion 324. The inwardlytapering sides 334, 336 meet at corresponding rounded ends.

FIGS. 18 and 19 illustrate cross-sectional views of another exampleimplementation of the shape memory alloy actuators 218 that can be usedto implement the actuators 218 of FIG. 5A or any of the actuatorsdisclosed herein. In the implementation shown, the actuator 218 includesa guide 338 defining an aperture 340 and including wire mounts 342. Theactuator 218 also includes an actuator rod 344 movable through theaperture 340 and including a plunger 346 at a distal end 348, a wireguide 350, and a spring seat 352. The wire guide 350 may be formed of awear-resistant material 353 to increase the useful life of the actuator218 by deterring the wire 230 from cutting into and/or otherwise wearingaway the actuator rod 344. If the wire 230 cuts into the actuator rod344, a length of the stroke of the actuator 218 may be reduced. Thematerial 353 may be a rigid and insulating material and resistant tofrictional wear.

A spring 354 is positioned between the guide 338 and the spring seat 352and urges the actuator rod 344 in a direction generally indicated byarrow 356. A shape memory alloy wire 230 is coupled to the wire mounts342 and positioned around the wire guides 350. To decrease the footprintof the actuator 218, an angle 358 at the interface with the wire guide350 is relatively small. In practice and as shown in FIG. 19 , the wire230 retracts when voltage is applied thereto causing the actuator rod344 to move between a first position and a second position and in adirection generally opposite that of arrow 356.

FIG. 20 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators 218 that can be usedto implement the actuators 218 of FIG. 5A or any of the actuatorsdisclosed. The actuator 218 is similar to the actuator 218 of FIGS. 18and 19 . However, in contrast, the actuator rod 34 includes a secondwire guide 360 and a second shape memory alloy wire 230 is coupled tothe wire mounts 342 and positioned around the second wire guide 360.Voltage is applied to the wire 230 sequentially in some implementationssuch that the voltage is applied to the first shape memory alloy wire230 to actuate the actuator 218 when voltage is not applied to thesecond shape memory alloy wire 230 and voltage is applied to the secondshape memory alloy wire 230 when voltage is not applied to the firstshape memory alloy wire 230. The first wire 230 may be used for a firsthalf of the useful life of the system 100 and the second wire 230 may beused for a second half of the useful life of the system 100. Put anotherway, voltage may no longer be applied to the first shape memory alloywire 230 after a threshold amount of time, after a threshold number ofcycles, or if the first shape memory alloy wire 230 is damaged and/orotherwise malfunctions. The system 100 may determine if the wire(s) 230is functional by, for example, measuring the impedance of the wire(s)230 and comparing the measured impedance value to a reference impedancevalue to determine if the measured impedance value is outside of athreshold of the reference impedance value indicative that the wire(s)230 is no longer functioning properly.

When the second wire 230 is to be used, the first wire may be retired(no longer used) and/or burned away using excess current. Longer wires230 have a longer useful life. However, by providing two or more wires230 that are shorter as shown in FIG. 20 , the same or a similar usefullife of the actuator 218 can be achieved while decreasing a height 362of the actuator 218. If the length of the wires 230 is increased, theuseful life of each of the wires 230 may be proportionally increased.While two wires 230 are shown, any number of wires 230 may be included(e.g., 3, 4, 5, etc.). Certain implementations however may havelimitations on the width of the actuator (amongst other limitations),thereby limiting the number of wires that may be placed next to eachother for a single actuator. Moreover, while applying voltage to thewires 230 in sequence is mentioned, voltage may be applied to the wires230 in parallel. Such an approach of applying voltage to both of thewires 230 at the same time may increase the force generated by eachactuator 218 while enabling a length of the wires 230 to decrease and/orallowing a diameter of the wires 230 to decrease. Shorter wires and/orwires having a smaller diameter may cool faster and, thus, allowcorresponding valves to be actuated faster.

FIG. 21 illustrates a cross-sectional views of another exampleimplementation of the shape memory alloy actuators 218 that can be usedto implement the actuators 218 of FIG. 5A or any of the actuatorsdisclosed. The actuator 218 of FIG. 21 is similar to the actuator 218 ofFIG. 20 . However, in contrast, the second wire 230 is coupled to wiremounts 342 of a second guide 364. Applying the voltage to the first wire230 advantageously retracts the first wire 230 and causes the actuatorrod 344 to move between the first position and the second position andin a direction generally indicated by arrow 366 and applying a voltageto the second shape memory alloy wire 230 retracts the second shapememory alloy wire 230 and causes the actuator rod 344 to move betweenthe second position and the first position and in a direction generallyopposite that of arrow 366. Using a second wire 230, as shown in FIG. 21, may reduce the time for the actuator 218 to return to the firstposition and, thus, reduce the time to actuate (open and/or close) theassociated membrane valve 144. Put another way, the secondary wire 230assists the spring 354 to close the associated membrane valve 144faster.

FIG. 22 illustrates a cross-sectional view of another exampleimplementation of the shape memory alloy actuators 218 that can be usedto implement the actuators 218 of FIG. 5A or any of the actuatorsdisclosed. The actuator 218 of FIG. 22 is similar to the actuator 218 ofFIG. 21 . However, in contrast, the first wire 230 is coupled to a firstwire guide 350 and the second wire 230 is coupled to a second wire guide350 spaced from the first wire guide 350. The first wire guide 350 ispositioned toward a distal end of the actuator rod 226 and the secondwire guide 350 is positioned toward a proximal end of the actuator rod226 such that the wires 230 cross one another but do not touch, therebyenabling a profile of the actuator 218 to be reduced. Moreover, in theimplementation shown, the first and second wires 230 are approximatelythe same length or at least the second wire 230 is longer than thesecond wire 230 of FIG. 21 .

FIG. 23 illustrates an isometric view of the second actuator assembly202 of the valve drive assembly 118 of FIG. 6 showing plunger portions244 of the actuator rods 226 extending through a printed circuit board214 and being actuatable to interface with an associated manifoldassembly 139.

FIG. 24 illustrates another isometric view of the second actuatorassembly 202 of FIG. 6 showing a housing 204, a plurality of actuatorrods 226, and a printed circuit board 214.

FIG. 25 illustrates another isometric view of a plurality of actuatorrods 226 including spring seats 363 of the second actuator assembly 202of FIG. 6 . Springs such as coil springs may be seated within the springseat 363 and positioned to act against the printed circuit board 214 andurge the actuator rods 226 in a direction generally indicated by arrow364.

FIGS. 26 and 27 are top and bottom views of another exampleimplementation of the manifold assembly 139 of FIG. 1 . In contrast tothe manifold assembly 139 of FIG. 4 , the manifold assembly 139 of FIGS.24 and 25 include volcano valves 366.

FIG. 28 is an isometric view of an example valve drive assembly 400 thatcan be used to implement the valve drive assembly 118 of FIGS. 1, 2, and3 . In the implementation shown, the valve drive assembly 400 includes ashape memory alloy actuator assembly 402 that can interface with themembrane valves 144 of the manifold assembly 139 of FIG. 1 . The valvedrive assembly 400 may have a height 404 of approximately 56 millimeters(mm) and a length 406 of approximately 76 mm. However, the valve driveassembly 400 may have different dimensions.

The actuator assembly 402 includes a housing 408 including a pair oflateral sides 409 each having a first end 410 and a second end 412 and atransverse section 413 coupling the lateral sides 206. The housing 204may be a H-shaped frame and the lateral sides 409 may be lateral wallsof the H-shaped frame. While the housing 408 is shown as a frame, thehousing 408 may include one or more solid blocks or pieces of materialthat define actuator rod bores. The actuator assembly 500 also includesa printed circuit board 414 coupled to the first end 410 of the housing408.

FIG. 29 is an isometric view of the printed circuit board 414 and aplurality of shape memory alloy actuators 416 of the actuator assembly402 of FIG. 28 . Each shape memory alloy actuator 416 includes a pair ofwire mounts 418 coupled to opposing sides 420, 422 of the printedcircuit board 414 and an actuator rod 424 including a wire guide 426.Each of the actuator rods 424 includes a side port 428 and an end face430 having a vacuum port 432 fluidically coupled to the side port 428and a plunger portion 434 that can be used to close a correspondingmembrane valve 144 by urging the membrane 154 against the valve seat158.

Referring back to FIG. 28 , the housing 408 of the actuator assembly 402includes slots 439 that allow the wires 230 of the actuators 416 to passthere through. The actuator assembly 402 also has an actuator manifoldassembly 440 coupled to the printed circuit board 414 and including abody 442 and a plurality of pneumatic lines 444. The body 442 has anoutlet port 446 and a plurality of inlet ports 448. The out port 446 ispositioned at an end 450 of the body 442 and the inlet ports 448 arepositioned on a side 452 of the body 442. The pneumatic lines 444 arecoupled between the side ports 428 of the actuator rods 424 and theinlet ports 448 of the actuator manifold assembly 440. The pneumaticlines 444 may be flexible fluidic lines to allow the pneumatic lines 444to move based on relative movement between the actuator rods 424 and thebody 442 of the actuator manifold assembly 440.

A pump such as the pump 166 of the system 100 of FIG. 1 can be connectedto the outlet port 446 and used to create a vacuum that draws airthrough the vacuum ports 432 and the side ports 428 of the correspondingactuators 416, through the inlet ports 448 of the actuator manifoldassembly 440, and out of the outlet port 446. The vacuum created at thevacuum ports 432 allows the vacuum ports 448 to sealingly engage themembrane 154 of the membrane valves 144 and move the membrane 154 awayfrom the valve seat 158 based on corresponding movement of the actuatorrod 424.

Each actuator rod 424 carries a target 454 (See, FIG. 29 ) and thehousing 408 and/or the printed circuit board 414 carries a sensor 456for each target 454. The target 454 may be magnetic (e.g., a magnet or aferromagnetic material) and the senor 456 may be a Hall-Effect sensorthat can be used to determine a stroke distance of the correspondingactuator rod 424, thereby allowing the actuator 416 to control a strokeof the actuator rod 424. The stroke may be between around 0.1 μm andaround 100 μm or another distance. While the actuator rod 424 ismentioned carrying the target 454 and the housing 408 and/or the printedcircuit board 414 is mentioned carrying the sensor 456, the actuator rod424 can carry the sensor 456 and the housing 408 and/or the printedcircuit board 414 can carry the target 454. Each of the actuator rods424 may additionally or alternatively include the sensor 456 and thecorresponding membrane valve 144 can include a target 454, therebyallowing the relative position between the end face 430 and the membrane154 to be determined. Responsive to a distance between the sensor 556carried by the actuator rod 424 and the target 454 carried by themembrane valve 144 being greater than a threshold value, the actuator416 can cause the actuator rod 424 to move toward the membrane 154 andfor the vacuum port 432 of the corresponding actuator 416 to sealingengage the membrane 154 in such implementations. Using the sensors 557to monitor a relative relationship between the actuator rods 424 and themembrane valves 144 allows the actuators 416 and/or the correspondingsystem 100 to determine when a sealing connection is no longer presentbetween the actuator rod 424 and the membrane 154.

Referring to FIG. 29 , each actuator rod 424 includes a portion 458 anda movable portion 460 that has a bore 462 receives the portion 458 anddefines a spring seat 464. The movable portion 460 may be used as avalve plug having the plunger portion 434 that selectively engages themembrane 154 of the corresponding membrane valve 144 to close themembrane valve 144. The actuator rod 424 interacts with surfaces of themovable portion 460 to guide movement of the movable portion 460 in adirection generally indicated by arrow 466 and between the firstposition and the second position. A biasing element 468 surrounds eachof the actuator rods 424 and biases the corresponding actuator rod 424in a direction generally opposite the direction generally indicated byarrow 466.

FIG. 30 is a top view of an example flow cell assembly 500 including amanifold assembly 502 and the flow cell 126 that can be used toimplement the flow cell assembly 106 of FIG. 1 . The manifold assembly502 includes membrane valves 504 that are formed by the manifold body148 and the membrane 154 that is coupled to a surface of the manifoldbody 148. The membrane valves 504 support high flow rate and reduceimpedance to 0.01 psi/min/mL, for example. For each membrane valve 504,the manifold body 148 includes a valve seat 506 and defines a chamber508 that is fluidically coupled to the reagent fluidic line 138 andpositioned between the reagent fluidic line 138 and the valve seat 506.A portion 510 of the membrane 154 covers the chamber 508. The chamber508 and the portion 510 of the membrane 154 have a width greater than awidth of the valve seat 506 in the implementation shown.

The width of the chamber 508 and the portion 510 increase the surfacearea of the chamber 508 and the portion 510, allows a greater force tobe exerted onto the membrane 154, and significantly reduce a crackingpressure when the actuators 416 open the corresponding membrane valve504. The cracking pressure may between about 0.4 pound per square inch(psi) and about 1.2 psi and, specially, about 0.45 psi, about 0.54 psi,about 0.74 psi, about 0.75 psi, about 0.77 psi, about 1.1 psi, about1.12 psi, about 1.2 psi, for example.

The chamber 508 and the portion 510 are shown being squircle shaped,tear-drop shaped, etc. Other shapes for the chamber 508 and the portion510 are suitable to achieve the reduced cracking pressure such as, forexample, oblong shaped, triangularly shaped, circular shaped, diamondshaped, stadium shaped, and/or other shapes that encourage flushing ofthe chamber 508 such as shapes with rounded corners.

The membrane valves 504 can be opened by the vacuum ports 432 of thecorresponding actuators 416 sealingly engaging the portion 510 of themembrane 154 and the actuator rods 424 moving between the first positionand the second position. The membrane valves 504 can be closed by theplunger portions 434 of the corresponding actuators 416 moving themembrane 154 from the second position to the first position and urgingthe membrane into engagement with the valve seat 506.

FIG. 31 is an isometric view of a portion of an example valve driveassembly 600 that can be used to implement the valve drive assembly 118of FIGS. 1, 2, and 3 . The valve drive assembly 600 of FIG. 31 issimilar to the valve drive assembly 400 of FIG. 28 . However, incontrast, each of the actuator rods 424 includes first and second sideports 428, 429 and the end face 430 of the actuator rods 424 has firstand second vacuum ports 432, 433 fluidically coupled to thecorresponding side port 428, 429. The plunger portion 434 is positionedbetween the first and second vacuum ports 432, 433.

FIG. 32 is an isometric view of the valve drive assembly 600 of FIG. 31including an actuator manifold assembly 602 coupled to the printedcircuit board 414 and including a body 604 and the pneumatic lines 444.The body 604 has the outlet port 446 positioned at the end 450 of thebody 604 and inlet ports 448 positioned on sides 452, 606 of the body442. The pneumatic lines 444 are coupled between the side ports 428 ofthe actuator rods 424 and corresponding inlet ports 448 of the actuatormanifold assembly 440. The valve drive assembly 600 may have a height607 of approximately 56 millimeters (mm), a length 608 of approximately76 mm, and a width 610 of approximately 55 mm. The valve drive assembly600 however may have different dimensions.

FIG. 33 is a detailed view of end face 430 of one of the actuator rods226 including the first and second vacuum ports 432, 433 with theplunger portion 434 positioned between the vacuum ports 432. Each of thevacuum ports 432, 433 in the implementation shown include a receptacle610 defined by a side wall 612 and a base 614 having an aperture 616that allows the vacuum ports 432, 433 to be fluidically coupled to thecorresponding side port 428. The receptacle 610 allows the vacuum ports432, 433 to apply a greater vacuum force on the membrane 154 of themembrane valves 144 and, thus, allows the membrane 154 to be more easilymoved by the actuators 416 away from the valve seat 158. The receptacles610 may alternatively be omitted and the bases 614 and the apertures 616may be placed immediately adjacent and/or in engagement with themembrane 154 of the membrane valves 144.

FIG. 34 is a top view of an example flow cell assembly 700 including amanifold assembly 702 and the flow cell 126 that can be used toimplement the flow cell assembly 106 of FIG. 1 . The manifold assembly702 includes membrane valves 704 that are similar to the membrane valves504 of the manifold assembly 502 of FIG. 30 . In contrast to themembrane valves 504 of the manifold assembly 502 of FIG. 30 , each ofthe membrane valves 704 includes first and second chambers 508, 509 andfirst and second portions 510, 511 of the membrane 154 that cover thefirst and second chambers 508, 509. The membrane valves 504 support highflow rate and bi-directional flow and reduce impedance. The valve seat506 is positioned between the first chamber 508 and the second chamber509.

The foregoing description is provided to enable a person skilled in theart to practice the various configurations described herein. While thesubject technology has been particularly described with reference to thevarious figures and configurations, it should be understood that theseare for illustration purposes only and should not be taken as limitingthe scope of the subject technology.

As used herein, an element or step recited in the singular and proceededwith the word “a” or “an” should be understood as not excluding pluralof said elements or steps, unless such exclusion is explicitly stated.Furthermore, references to “one implementation” are not intended to beinterpreted as excluding the existence of additional implementationsthat also incorporate the recited features. Moreover, unless explicitlystated to the contrary, implementations “comprising,” “including,” or“having” an element or a plurality of elements having a particularproperty may include additional elements whether or not they have thatproperty. Moreover, the terms “comprising,” including, “having,” or thelike are interchangeably used herein.

The terms “substantially,” “approximately,” and “about” used throughoutthis Specification are used to describe and account for smallfluctuations, such as due to variations in processing. For example, theycan refer to less than or equal to ±5%, such as less than or equal to±2%, such as less than or equal to ±1%, such as less than or equal to±0.5%, such as less than or equal to ±0.2%, such as less than or equalto ±0.1%, such as less than or equal to ±0.05%.

There may be many other ways to implement the subject technology.Various functions and elements described herein may be partitioneddifferently from those shown without departing from the scope of thesubject technology. Various modifications to these implementations maybe readily apparent to those skilled in the art, and generic principlesdefined herein may be applied to other implementations. Thus, manychanges and modifications may be made to the subject technology, by onehaving ordinary skill in the art, without departing from the scope ofthe subject technology. For instance, different numbers of a givenmodule or unit may be employed, a different type or types of a givenmodule or unit may be employed, a given module or unit may be added, ora given module or unit may be omitted.

Underlined and/or italicized headings and subheadings are used forconvenience only, do not limit the subject technology, and are notreferred to in connection with the interpretation of the description ofthe subject technology. All structural and functional equivalents to theelements of the various implementations described throughout thisdisclosure that are known or later come to be known to those of ordinaryskill in the art are expressly incorporated herein by reference andintended to be encompassed by the subject technology. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the above description.

It should be appreciated that all combinations of the foregoing conceptsand additional concepts discussed in greater detail below (provided suchconcepts are not mutually inconsistent) are contemplated as being partof the inventive subject matter disclosed herein. In particular, allcombinations of claimed subject matter appearing at the end of thisdisclosure are contemplated as being part of the inventive subjectmatter disclosed herein.

1. An apparatus, comprising: a shape memory alloy actuator assembly,comprising: a housing; a printed circuit board; a plurality of shapememory alloy actuators, each shape memory alloy actuator comprising: apair of wire mounts coupled to opposing sides of the printed circuitboard; an actuator rod comprising a wire guide; and a shape memory alloywire coupled to the wire mounts and positioned around the wire guide,wherein applying a voltage to the shape memory alloy wire retracts theshape memory alloy wire and causes the corresponding actuator rod tomove between a first position and a second position, and wherein theactuator rods are guided between the first position and the secondposition.
 2. The apparatus of claim 1, further comprising guideapertures and each of the actuator rods have a plunger portioncorresponding to one of the guide apertures.
 3. The apparatus of claim2, wherein the actuator rods and the guide apertures interact to guidethe actuator rods between the first position and the second position 4.The apparatus of claim 2, further comprising an end plate coupled to thehousing and defining the guide apertures.
 5. The apparatus of claim 2,wherein the printed circuit board defines the guide apertures.
 6. Theapparatus of claim 5, wherein the actuator rods extend through the guideapertures of the printed circuit board.
 7. The apparatus of claim 1,further comprising springs, wherein the actuator rods each comprise aspring seat against which the corresponding spring seats.
 8. Theapparatus of claim 7, wherein the springs are positioned to act againstthe printed circuit board.
 9. The apparatus of claim 8, wherein theprinted circuit board comprises a longitudinal axis and the springs havelongitudinal axes, the longitudinal axes of the springs beingsubstantially perpendicular to the longitudinal axis of the printedcircuit board.
 10. The apparatus of claim 7, wherein the actuator rodsdefine a U-shaped portion that comprises the spring seat.
 11. Theapparatus of claim 10, wherein the springs are positioned within thecorresponding U-shaped portion of the actuator rods.
 12. The apparatusof claim 1, wherein each shape memory alloy actuator includes a sensoror a target carried by the actuator rod and the housing carries theother of the sensor or the target.
 13. A method, comprising: applying avoltage to a shape memory alloy wire of a shape memory alloy actuatorassembly; moving a corresponding actuator rod between a first positionand a second position in response to the voltage being applied; andactuating a valve of a flow cell assembly based on the movement of theactuator rod.
 14. The method of claim 13, wherein moving the actuatorrod between the first position and the second position comprises movingthe actuator rod toward the valve.
 15. The method of claim 13, whereinmoving the actuator rod between the first position and the secondposition comprises moving the actuator rod away the valve.
 16. Themethod of claim 13, further comprising holding the actuator rod in thesecond position.
 17. The method of claim 16, wherein holding theactuator rod in the second position comprises continuing to apply thevoltage to the shape memory alloy wire.
 18. The method of claim 13,wherein the shape memory allow assembly comprises a housing, a printedcircuit board, and a shape memory alloy actuator, the shape memory alloyactuator comprising: a pair of wire mounts coupled to opposing sides ofthe printed circuit board; an actuator rod comprising a wire guide; andthe shape memory alloy wire coupled to the wire mounts and positionedaround the wire guide.
 19. The method of claim 13, wherein the valvecomprises a membrane valve.
 20. The method of claim 13, wherein the flowcell assembly comprises a flow cell inlet, a flow cell outlet, a flowcell, a reagent fluidic line, and the valve, the valve selectivelyfluidically coupling flow cell and the reagent fluidic line.
 21. Anapparatus, comprising: a system comprising a receptacle and ashape-memory alloy actuator, the shape-memory alloy actuator comprising:a guide including wire mounts; an actuator rod including a plunger at adistal end, a wire guide, and a spring seat; a spring positioned toengage the spring seat; a shape memory alloy wire coupled to the wiremounts and positioned around the wire guide; and wherein applying avoltage to the shape memory alloy wire retracts the shape memory alloywire and causes the actuator rod to move between a first position and asecond position.
 22. The apparatus of claim 21, wherein the guidecomprises a printed circuit board.
 23. The apparatus of claim 21,wherein the spring is positioned between the guide and the spring seat.24-40. (canceled)